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Titolo:
SJ-3366, a unique and highly potent nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1) that also inhibits HIV-2
Autore:
Buckheit, RW; Watson, K; Fliakas-Boltz, V; Russell, J; Loftus, TL; Osterling, MC; Turpin, JA; Pallansch, LA; White, EL; Lee, JW; Lee, SH; Oh, JW; Kwon, HS; Chung, SG; Cho, EH;
Indirizzi:
So Res Inst, Infect Dis Res Dept, Frederick, MD 21701 USA So Res Inst Frederick MD USA 21701 Dis Res Dept, Frederick, MD 21701 USA So Res Inst, Dept Biochem, Birmingham, AL 35255 USA So Res Inst Birmingham AL USA 35255 ept Biochem, Birmingham, AL 35255 USA Samjin Pharmaceut Co Ltd, Seoul, South Korea Samjin Pharmaceut Co Ltd Seoul South Korea t Co Ltd, Seoul, South Korea
Titolo Testata:
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
fascicolo: 2, volume: 45, anno: 2001,
pagine: 393 - 400
SICI:
0066-4804(200102)45:2<393:SAUAHP>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
DRUG-RESISTANT VARIANTS; OXATHIIN CARBOXANILIDE; NUCLEOSIDE ANALOGS; 1-<(2-HYDROXYETHOXY)METHYL>-6-(PHENYLTHIO)THYMINE; DERIVATIVES; REPLICATION; NEVIRAPINE; BINDING; NNRTIS; 5'-TRIPHOSPHATES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Buckheit, RW So Res Inst, Infect Dis Res Dept, 431 Aviat Way, Frederick, MD 21701 USA So Res Inst 431 Aviat Way Frederick MD USA 21701 MD 21701 USA
Citazione:
R.W. Buckheit et al., "SJ-3366, a unique and highly potent nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1) that also inhibits HIV-2", ANTIM AG CH, 45(2), 2001, pp. 393-400

Abstract

We have identified and characterized a potent new nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) of human immunodeficiency virus type 1 (HIV-1) that also is active against HIV-2 and which interferes with virus replication by two distinct mechanisms. 1-(3-Cyclopenten-1-yl)methyl-6-(3,5-dimenthyl-benzoyl)-5-ethyl-2,4-pyrimidinedione (SJ-3366) inhibits HIV-1 replication at concentrations of approximately 1 nM, with a therapeutic index of greater than 4 x 10(6). The efficacy and toxicity of SJ-3366 are consistent when evaluated with established or fresh human cells, and the compound is equipotent against all strains of HIV-1 evaluated, including syncytium-inducing, non-syncytium-inducing, monocyte/macrophage-tropic, and subtype virus strains. Distinct from other members of the pharmacologic class of NNRTIs, SJ-3366 inhibited laboratory and clinical strains of HIV-2 at a concentration of approximately 150 nM, yielding a therapeutic index of approximately 20,000. Like most NNRTIs, the compound was less active when challenged with HIV-1 strains possessing the Y181C, K103N, and Y188C amino acid changes in the RT and selected for a virus with a Y181C amino acid change in the RTafter five tissue culture passages in the presence of the compound. In combination anti-HIV assays with nucleoside and nonnucleoside RT and protease inhibitors, additive interactions occurred with all compounds tested with the exception of dideoxyinosine, with which a synergistic interaction was found. Biochemically, SJ-3366 exhibited a K-i value of 3.2 nM, with a mixed mechanism of inhibition against HIV-1 RT, but it did not inhibit HIV-2 RT, SJ-3366 also inhibited the entry of both HIV-1 and HIV-2 into target cells. On the basis of its therapeutic index and multiple mechanisms of anti-HIV action, SJ-3366 represents an exciting new compound for use in HIV-infected individuals.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/09/20 alle ore 08:08:09